In September 2023， the Measures for Scientific and Technological Ethics Review （Trial Implementation） was issued， revising the provisions related to the simplified procedure for ethical review in Chapter 3， Section 3. This revision of these provisions provides systematic guarantees for further optimizing ethical review work， ensuring that ethical review procedure is well-regulated， and improving scientific research efficiency. The “simplified procedure” does not mean reducing the quality and requirements of the review. Instead， based on always following internationally recognized ethical standards and emphasizing not violating national laws and regulations， improving the efficiency of ethical review and subsequent research work， and promoting the development of life sciences and medical research involving humans. In practical work， it introduces numerous new opportunities and challenges for the improvement of ethics review ability， such as new tests on the judgment and decision-making power of ethics committees， how to ensure the reliability and controllability of the conditions related to the simplified review procedure， and how to determine the basic conditions for adopting the simplified review procedure for review. Therefore， to actively respond to the challenges and possible risks brought by the simplified procedure review， efforts should be made to achieve three “unifications”， including the unification of researchers’ moral autonomy and the heteronomy of supervision implemented by relevant departments； the unification of the standard formulation of the simplified procedure review and the review work in practice； and the unification of ethical responsibility and legal responsibility.

Background/Aims: Early detection and effective prognosis prediction in patients with hepatocellular carcinoma (HCC) provide an avenue for survival improvement, yet more effective approaches are greatly needed. We sought to develop the detection and prognosis models with ultra-sensitivity and low cost based on fragmentomic features of circulating cell free mtDNA (ccf-mtDNA). Methods: Capture-based mtDNA sequencing was carried out in plasma cell-free DNA samples from 1168 participants, including 571 patients with HCC, 301 patients with chronic hepatitis B or liver cirrhosis (CHB/LC) and 296 healthy controls (HC). Results: The systematic analysis revealed significantly aberrant fragmentomic features of ccf-mtDNA in HCC group when compared with CHB/LC and HC groups. Moreover, we constructed a random forest algorithm-based HCC detection model by utilizing ccf-mtDNA fragmentomic features. Both internal and two external validation cohorts demonstrated the excellent capacity of our model in distinguishing early HCC patients from HC and highrisk population with CHB/LC, with AUC exceeding 0.983 and 0.981, sensitivity over 89.6% and 89.61%, and specificity over 98.20% and 95.00%, respectively, greatly surpassing the performance of alpha-fetoprotein (AFP) and mtDNA copy number. We also developed an HCC prognosis prediction model by LASSO-Cox regression to select 20 fragmentomic features, which exhibited exceptional ability in predicting 1-year, 2-year and 3-year survival (AUC=0.8333, 0.8145 and 0.7958 for validation cohort, respectively). Conclusions We have developed and validated a high-performing and low-cost approach in a large clinical cohort based on aberrant ccf-mtDNA fragmentomic features with promising clinical translational application for the early detection and prognosis prediction of HCC patients.

BACKGROUND:Our previous study found that Modified Erxian Pill could alleviate inflammation in collagen-induced arthritis rats,but its mechanism needs to be further verified. OBJECTIVE:To analyze the components absorbed in the blood of Modified Erxian Pill,and observe the effect of the drug-containing serum of Modified Erxian Pill on pyroptosis of J774A.1 macrophages. METHODS:(1)Analysis of components absorbed in the blood of Modified Erxian Pill:Ultra-high performance liquid chromatography-high resolution mass spectrometry was used to detect and identify Modified Erxian Pill and its components absorbed in the blood.(2)Effect of the drug-containing serum of Modified Erxian Pill on pyroptosis of J774A.1 macrophages:Molecular docking technology was used to initially verify the sesquiterpenoids and NLRP3 in components absorbed in the blood of Modified Erxian Pill.J774A.1 macrophages were randomly divided into blank control group,lipopolysaccharide+adenosine triphosphate group,and lipopolysaccharide+adenosine triphosphate+Modified Erxian Pill with low(2.5%),medium(5%),and high(10%)dose groups.The release of lactate dehydrogenase in the cell supernatant of each group was detected according to the kit instructions.The levels of interleukin-1β and interleukin-18 in cell supernatant were detected in each group by ELISA.The cell membrane damage was detected by Hoechst/PI staining.The expression levels of NLRP3,Caspase-1,GSDMD,and GSDMD-N protein in the cells of each group were detected by western blot assay. RESULTS AND CONCLUSION:(1)A total of 32 active components of Modified Erxian Pill were identified,and 21 components entered the blood.The main components into blood included a variety of sesquiterpenoids.(2)Molecular docking results showed that 3-O-Acetyl-13-deoxyphomenone,Incensol oxide,Atractylenolide III,Rupestonic acid,and 3,7-Dihydroxy-9,11-eremophiladien-8-one had good binding activity with NLRP3.(3)Compared with the blank control group,lactate dehydrogenase activity and the expression levels of interleukin-1β and interleukin-18 were significantly increased in cell supernatant of lipopolysaccharide+adenosine triphosphate group(P<0.001).Hoechst/PI staining showed that the number of PI-positive cells was significantly increased.After the intervention of lipopolysaccharide+adenosine triphosphate+Modified Erxian Pill group,all of them showed different degrees of reduction.(4)Compared with the blank control group,NLRP3,Caspase-1,GSDMD,and GSDMD-N protein expression levels were significantly increased in the lipopolysaccharide+adenosine triphosphate group(P<0.05).Compared with lipopolysaccharide+adenosine triphosphate group,the protein expressions of NLRP3,Caspase-1,GSDMD,and GSDMD-N were significantly decreased in the lipopolysaccharide+adenosine triphosphate+Modified Erxian Pill group(P<0.05),and had a certain dose dependence.These findings verify that the drug-containing serum of Modified Erxian Pill may inhibit the pyroptosis of J774A.1 macrophages by regulating the NLRP3/Caspase-1/GSDMD pathway.

Background/Aims: Early detection and effective prognosis prediction in patients with hepatocellular carcinoma (HCC) provide an avenue for survival improvement, yet more effective approaches are greatly needed. We sought to develop the detection and prognosis models with ultra-sensitivity and low cost based on fragmentomic features of circulating cell free mtDNA (ccf-mtDNA). Methods: Capture-based mtDNA sequencing was carried out in plasma cell-free DNA samples from 1168 participants, including 571 patients with HCC, 301 patients with chronic hepatitis B or liver cirrhosis (CHB/LC) and 296 healthy controls (HC). Results: The systematic analysis revealed significantly aberrant fragmentomic features of ccf-mtDNA in HCC group when compared with CHB/LC and HC groups. Moreover, we constructed a random forest algorithm-based HCC detection model by utilizing ccf-mtDNA fragmentomic features. Both internal and two external validation cohorts demonstrated the excellent capacity of our model in distinguishing early HCC patients from HC and highrisk population with CHB/LC, with AUC exceeding 0.983 and 0.981, sensitivity over 89.6% and 89.61%, and specificity over 98.20% and 95.00%, respectively, greatly surpassing the performance of alpha-fetoprotein (AFP) and mtDNA copy number. We also developed an HCC prognosis prediction model by LASSO-Cox regression to select 20 fragmentomic features, which exhibited exceptional ability in predicting 1-year, 2-year and 3-year survival (AUC=0.8333, 0.8145 and 0.7958 for validation cohort, respectively). Conclusions We have developed and validated a high-performing and low-cost approach in a large clinical cohort based on aberrant ccf-mtDNA fragmentomic features with promising clinical translational application for the early detection and prognosis prediction of HCC patients.

Background/Aims: Early detection and effective prognosis prediction in patients with hepatocellular carcinoma (HCC) provide an avenue for survival improvement, yet more effective approaches are greatly needed. We sought to develop the detection and prognosis models with ultra-sensitivity and low cost based on fragmentomic features of circulating cell free mtDNA (ccf-mtDNA). Methods: Capture-based mtDNA sequencing was carried out in plasma cell-free DNA samples from 1168 participants, including 571 patients with HCC, 301 patients with chronic hepatitis B or liver cirrhosis (CHB/LC) and 296 healthy controls (HC). Results: The systematic analysis revealed significantly aberrant fragmentomic features of ccf-mtDNA in HCC group when compared with CHB/LC and HC groups. Moreover, we constructed a random forest algorithm-based HCC detection model by utilizing ccf-mtDNA fragmentomic features. Both internal and two external validation cohorts demonstrated the excellent capacity of our model in distinguishing early HCC patients from HC and highrisk population with CHB/LC, with AUC exceeding 0.983 and 0.981, sensitivity over 89.6% and 89.61%, and specificity over 98.20% and 95.00%, respectively, greatly surpassing the performance of alpha-fetoprotein (AFP) and mtDNA copy number. We also developed an HCC prognosis prediction model by LASSO-Cox regression to select 20 fragmentomic features, which exhibited exceptional ability in predicting 1-year, 2-year and 3-year survival (AUC=0.8333, 0.8145 and 0.7958 for validation cohort, respectively). Conclusions We have developed and validated a high-performing and low-cost approach in a large clinical cohort based on aberrant ccf-mtDNA fragmentomic features with promising clinical translational application for the early detection and prognosis prediction of HCC patients.

The clinical data of a case of Niemann-Pick disease type C diagnosed at Beijing Children′s Hospital, Capital Medical University on December 22, 2017 were retrospectively analyzed.The patient, male, 1 year and 28 days old, was admitted to the hospital primarily due to intermittent fever, cough and dyspnea for 8 months, and hepatosplenomegaly for 20 days.The patient initially presented with cough, expectoration, and wheezing, followed by hypotonia and delayed motor development.At the age of 1 year, the child developed hepatosplenomegaly and diffuse interstitial changes in both lungs.At the age of 3 years, the child had obvious vertical supranuclear gaze palsy and gelastic cataplexy, followed by dysarthria and dysphagia.The foam cells were found by bone marrow cytology, while sphingomyelinase and glucocerebrosidase were normal, so Niemann-Pick disease type A/B and Gaucher disease were excluded.Finally, genetic testing revealed two pathogenic mutations in the NPC1 gene, so Niemann-Pick disease type C was confirmed.Miglustat treatment began when the child was 3 years old, and vertical supranuclear gaze palsy and gelastic cataplexy improved for a while, but then the neurological symptoms worsened again, with dysphagia and dyspnea gradually increasing, and finally he died at the age of 4 years and 11 months.

A case of idiopathic hypertrophic spinal pachymeningitis is reported. The patient was a middle-aged female, with the course of disease more than 1 year. Clinical manifestations included recurrent fever,headache and backache, and the magnetic resonance imaging showed diffuse enhancement and thickening of the spinal dura mater. Dural biopsy pathology finally confirmed hypertrophic spinal pachymeningitis. After treatment with surgery and immunotherapy, the patient′s clinical symptoms improved.

ObjectiveTo evaluate the Chinese guidelines and consensus of rehabilitation medicine published in the medical journals in 2022 using Scientific, Transparent and Applicable Rankings (STAR). MethodsGuidelines and consensus which were developed by Chinese institutions or led by Chinese scholars were retrieved in databases of CNKI, Wanfang Data, CBM, Chinese Medical Journal Network, PubMed and Web of Science, in 2022, followed by screening for rehabilitation medicine field. The literature were rated with STAR. ResultsSeven guidelines and eleven consensuses were included. The STAR scores ranged from 11.7 to 69.6, with a median score of 25.9 and mean score of 28.3. There was a significant difference in the total score between guidelines and consensus (U = 12.000, P = 0.014). The score ratio was high in the domains of recommendations (73.6%), evidence (39.5%) and others (33.3%), while it was low in the domains of protocol (1.4%), clinical questions (12.5%) and conflicts of interest (13.9%). The score ratio was high in the items of listing the institutional affiliations of all individuals involved in developing the guideline (94.4%), identifying the references for evidence supporting the main recommendations (94.4%), indicating the considerations (e.g., adverse effects) in clinical practice when implementing the recommendations (88.9%), and making the recommendations clearly identifiable, e.g., in a table, or using enlarged or bold fonts (75%); and it was low in the items of describing the role of funder(s) in the guideline development (0), indicating information about the evaluation and management of conflicts of interest (0), providing tailored editions of the guidelines for different groups of target users (0), presenting the guideline or recommendations visually, such as with figures or videos (0), providing details of the guideline protocol (2.8%), assessing the risk of bias or methodological quality of the included studies (2.8%), describing the responsibilities of all individuals or sub-groups involved in developing the guideline (5.6%), indicating how the clinical questions were selected and sorted (5.6%), formating clinical questions in PICO or other formats (5.6%), making the guideline accessible through multiple platforms (5.6%), and declaring that the funder(s) did not influence the guideline's recommendations (8.3%). ConclusionThe quality of current clinical practice guidelines and consensus of rehabilitation medicine is poor, which should be developed in accordance with the relevant standards.

Objective To explore the distribution of common syndromes in sepsis based on literature data mining.Methods The literature related to sepsis symptoms analysis included in China National Knowledge Infrastructure(CNKI),Chinese Biomedical Literature Database(CBM),VIP database(VIP)and Wanfang Data were searched by computer to extract relevant information and establish a database.Analysis of common syndromes and symptoms of sepsis by frequency statistics.Based on LTM-EAST algorithm of two-step hidden tree analysis,a symptom hidden structure model with frequency≥10 was constructed by Latern 5.0 software,and potential syndromes were inferred through comprehensive clustering.Symptoms with frequency＞5%were selected for factor analysis,common factors were extracted for further systematic cluster analysis,and potential syndromes were inferred according to the results.Based on the above results,the common syndromes and clinical characteristics of sepsis were analyzed.Results A total of 792 literatures and 961 syndromes records and 877 symptoms records were included,involving 48 syndromes after the regulation,with high frequency of pattern of blood stasis,pattern of yangming fu-organ excess,pattern of internal block of the heart orifices due to phlegm and heat,pattern of yang prostration,etc.The frequencies were 12.70%(122/961),9.68%(93/961),9.47%(91/961)and 7.80%(75/961).It involved 179 symptoms after the regulation,including high fever,red tongue,thirst,dysphoria,etc.The frequencies were 27.82%(244/877),27.36%(240/877),27.25%(239/877),25.54%(244/877).Forty-three hidden variables were obtained through implicit structure analysis,according to professional knowledge,12 potential syndromes were obtained by comprehensive clustering,including pattern of blood stasis,pattern of yangming fu-organ excess,pattern of phlegm and heat congesting in the lung,pattern of fire toxin entering the nutrient phase,pattern of Yin deficiency with exuberant heat,pattern of Yang prostration,pattern of Qi deficiency,pattern of Yang deficiency,pattern of turbid phlegm obstructing the lung,pattern of damp-heat encumbering the spleen,pattern of intense exuberant heat toxin,pattern of pathogenic factors repressing defensive Qi of lung.Twenty-five common factors were obtained by factor analysis,and 12 potential syndromes were inferred by systematic clustering,including pattern of heart-Yang deficiency,pattern of phlegm and heat congesting in the lung,pattern of yangming fu-organ excess,pattern of Yang prostration,pattern of intense exuberant heat toxin,pattern of Yang deficiency in spleen and kidney,pattern of Qi deficiency,pattern of phlegm and heat damaging Yin,pattern of Qi deficiency with blood stasis,pattern of Qi and Yin deficiency,pattern of pathogenic factors repressing defensive Qi of lung,and pattern of heat sinking into the pericardium.According to the standard of common traditional Chinese medicine(TCM)syndromes and their symptom characteristics,9 common syndromes of sepsis were finally obtained,including pattern of intense exuberant heat toxin,blood stasis,pattern of yangming fu-organ excess,pattern of phlegm and heat congesting in the lung,pattern of fire toxin entering,pattern of pathogenic factors repressing defensive Qi of lung,pattern of Qi and Yin deficiency,pattern of Qi deficiency,pattern of Yang prostration.Conclusion The symptoms and characteristics of common syndromes of sepsis are significant,which can provide evidence for the syndrome diagnosis standard of sepsis.

Objective To explore the distribution of traditional Chinese medicine basic syndromes in sepsis,and to provide evidence for the establishment of diagnostic criteria of sepsis syndromes.Methods Literatures related to sepsis syndrome included in China National Knowledge Infrastructure(CNKI),Wanfang Data,VIP database(VIP)and Chinese Biomedical Literature Database(CBM)databases were searched from the establishment of the database to May 30,2020.Screen the literature and extract data,establish a database for statistical description and analysis of syndrome elements,basic syndromes and symptoms.Analyze the association rule of syndrome elements based on the Apriori algorithm.Based on the two-step hidden tree analysis LTM-EAST algorithm,a symptom latent structure model was constructed,and a comprehensive cluster analysis and model interpretation were performed.Results A total of 383 articles related to sepsis syndromes were included,involving 31 basic syndromes,146 symptoms and 29 syndromes elements.The basic syndromes with frequencies≥5%and cumulative composition ratios≥75%were heat and toxin syndrome,blood stasis syndrome,Yin deficiency syndrome,heat and closing syndrome,Qi deficiency syndrome,phlegm and heat syndrome,Yang prostration syndrome,Fu-organ excess syndrome,and Yang deficiency syndrome.Perform the association rule analysis on syndrome elements with a frequency＞5,obtaining 8 strong association rules,and inferring 7 basic syndromes,including Fu-organ excess syndrome,heat and toxin syndrome,heat and closing syndrome,phlegm clouding the heart syndrome,heat disturbing the heart spirit syndrome,phlegm and heat syndrome,phlegm block syndrome.The symptoms with frequency＞5 were analyzed by hidden structure,41 hidden variables and 82 hidden categories were obtained,and 11 comprehensive clustering models were obtained through comprehensive clustering.Eleven basic syndromes were inferred,including heat and toxin syndrome,blood stasis syndrome,Yin deficiency syndrome,heat and closing syndrome,Qi deficiency syndrome,phlegm and heat syndrome,Yang prostration syndrome,Fu-organ excess syndrome,Yang deficiency syndrome,Yingfen syndrome,and phlegm-dampness syndrome.Combined with all of methods above,9 basic syndromes,heat and toxin syndrome,blood stasis syndrome,Yin deficiency syndrome,heat and closing syndrome,Qi deficiency syndrome,phlegm and heat syndrome,Yang prostration syndrome,Fu-organ excess syndrome,and Yang deficiency syndrome were finally confirmed.Conclusion There are 9 common basic syndromes of sepsis,and the sufficient syndromes are mainly heat and toxin syndrome,blood stasis syndrome,heat and closing syndrome,phlegm and heat syndrome and Fu-organ excess syndrome,while the deficiency syndromes are mainly Yin deficiency syndrome,Qi deficiency syndrome,Yang prostration syndrome,and Yang deficiency syndrome,with each basic syndrome having certain symptom characteristics.